The aim of this project is to understand the physiological and ultrastructural basis of the blood-brain barrier, and to modify the permeability restriction of the barrier for use in pharmacotherapy. We have (a) elaborated the theory and provided morphological and physiological demonstration of osmotic opening of the barrier, (b) refined the technique of osmotic opening so that it can be accomplished without producing brain edema or apparent neurological damage, (c) used osmotic opening to increase barrier permeability to circulating measles antibody in the rhesus monkey, (d) related differences in neurotoxicity of X-ray contrast agents to differences in barrier permeability, (e) initiated studies on barrier opening by acute hypertension, and (f) modified the permeability of the blood-aqueous and blood-vitreous barriers of the eye with hypertonic solutions.